The present disclosure relates to microfluidic methods and devices for forming structures from polymers and biopolymers. More particularly, the present disclosure relates to tubular biopolymer structures for biological applications. The present disclosure also relates to applications that include 3D cell culture and microphysiological systems for drug discovery, biomanufacturing of drugs and fuels, as well as molecular gastronomy.
Perfusable soft materials with complex geometries and defined heterotypic composition are abundant in nature. These tissues often possess a hierarchical architecture at length scales ranging from large molecules to several millimeters and often alter their structure and morphology over time. Examples of soft tissues in the body with similar composition and geometries include blood vessels (i.e. arteries, veins, and capillaries), the intestinal mucosa and airways (e.g. submucosa and bronchioles). Very few approaches exist which allow the spatial organization of soft matter into 3D tissues, specifically perfusable tubes, in a scalable format. The continuous production of microscale fibers and tubes is of particular interest in the generation of tissue engineered blood vessels and in cell-encapsulation for soft tissue applications1,2.
The lack of scalable techniques to achieve a heterotypic composition is particularly evident at the micrometer to millimeter length scales which are of key importance for nutrient transport, cell-cell and cell-matrix interactions. Previously employed top-down fabrication approaches start from planar substrates and employ a series of processing steps (e.g., lithography, printing, engraving or direct writing) to ultimately obtain the desired heterotypic characteristics3. Bottom-up approaches are also possible, where microscale zero-dimensional and one-dimensional building blocks are assembled to form planar and 3-D assemblies4.
There is great interest in technologies that enable the vascularization of bulk materials and engineered tissues while displaying adequate diffusive transport, displaying tunable mechanical and chemical properties, and displaying suitable biocompatibility and degradation rates7,8. Control of these factors is required to recapitulate the complex, highly localized, and dynamically evolving mechanical and chemical milieu of in vivo tissue properties. Highly organized 3D synthetic and natural extracellular matrix protein networks have been identified as key components of biomaterials needed to mimic the complex regulatory characteristics and temporal and spatial complexity of native tissues9,10. Achieving 3D spatio-temporal control of material geometry and properties presents a significant challenge in the formation of bioactive scaffolds.